Rectifying disordered brain dynamics to improve cognition in schizophrenia

Although most of us are more familiar with the spectacular psychotic symptoms, such as hallucinations and delusions, that characterize schizophrenia, it is the cognitive deficits that drive much of the disability seen in this illness, serving as a “glass ceiling” that limits social and occupational functioning in patients with the illness (1). Impaired cognition is largely unresponsive to antipsychotic treatment, and despite a very significant investment by the pharmaceutical industry for over a decade, no proven pharmacological treatments have been found for this disabling aspect of the illness. The study by Reinhart et al. (2) in PNAS takes a cognitive neuroscience approach to pursue an entirely new avenue for the treatment of impaired cognition and associated functional disability in schizophrenia. Reinhart et al.’s (2) work is informed by an extensive literature on the neural mechanisms that underlie dynamic cognitive control (the moment-to-moment adjustments in attention that characterize flexible cognitive functioning) that have been shown to be disrupted in schizophrenia (3). Studies using EEG and functional MRI in healthy individuals have shown that this aspect of cognitive control depends upon interactions between the medial prefrontal cortex (PFC, specifically the dorsal anterior cingulate cortex and adjacent presupplementary motor area), which becomes active during brain states such as errors, conflict, or losses when increased cognitive control is necessary for successful goal-directed performance, and lateral prefrontal systems, which then become more engaged to enhance the level of cognitive control during subsequent performance (4). Phase coherence of synchronously firing population neuronal activity in the theta (4–8 Hz) range has been proposed as a mechanism for detecting the need for increased control, as well as for linking medial to lateral prefrontal functioning to dynamically adjust performance (5). As one aspect of their cognitive control deficit, individuals with schizophrenia show impaired dynamic control as indexed by reduced …